Development of sodium permeability inactivation in nodal membranes.

1. The time course of inactivation of the sodium permeability was studied in myelinated nerve fibres of Xenopus laevis using the voltage-clamp technique of Nonner (1969). The potassium currents were blocked by 10 mM-tetraethylammonium chloride (TEA). The remaining currents were corrected for leakage and capacity currents. 2. The decay of the sodium current was double-exponential confirming Chiu's (1977) findings The slower time constant was observed in TEA-free solutions by clamping to VK in high potassium concentrations. 3. The fast time constant was similar to tau h of Frankenhaeuser (1960), whereas the slower time constant was about four times larger and also decreased with increasing depolarization. 4. Arrhenius plots of both time constants can be well approximated by straight lines for temperatures between 0 and 25 degrees C. 5. The entire sodium current induced by single voltage-clamp pulses was fitted by a non-linear least-square routine to the Frankenhaeuser-Huxley equations extended by Chiu's three-state kinetics. With rare exceptions for potentials between 37 and 70 mV the fit was better without a delay in the onset of the inactivation of the sodium current. 6. The time course of inactivation was also studied in two-pulse experiments where a prepulse of varying duration was directly followed by a test pulse. The peak sodium currents were normalized by the associated peak currents without a prepulse. 7. The relative peak sodium current as a function of the prepulse duration had a sigmoid time course. The early deviation from an exponential decay is due to the activation arising during the prepulse and is implicit in the classical equations quoted above. It is therefore not necessarily a sign of a delay in the inactivation process. 8. To eliminate errors due to activation in two-pulse experiments, the decaying part of the test sodium currents was extrapolated back to the onset of the test pulse. These current values at t = 0 plotted as a function of the prepulse duration revealed no delay at the beginning of inactivation. Within the accuracy of our measurements a possible delay of more than 100 microseconds (at 5-10 degrees C) could be excluded.